Physicists at
the University of California, San Diego have discovered a neural
circuit in rats that could provide a powerful model for understanding
a neurological condition known as blepharospasm—uncontrolled
eye blinking that affects 50,000 people in the U.S. and leaves
some patients functionally blind.

A
rat’s whiskers
Credit: Samar B. Metha, UCSD

In the February 3 issue
of the journal Neuron, the researchers, Quoc-Thang
Nguyen and David Kleinfeld, describe the brain circuit, which
coordinates sensory inputs and muscle activity in rats’
whiskers. It is the first discovery of a reflex circuit that
functions to boost the amount of incoming sensory information.
Because the neural wiring of the rat whiskers appears to be
identical to the circuit that controls eyeblinking in humans,
the UCSD scientists believe it could be used for pioneering
new treatments for blepharospasm.

“We have been
studying the rat whisker system as an example to help us understand
how sensory systems control where the sensors are in space and
how the sensors are moved,” said Nguyen, an assistant
project scientist in UCSD’s physics department. “Our
study is the first to find a neural circuit responsible for
keeping sensors on an object during active touch.”

“We hope that
this finding will help push the field from a focus biased by
anatomy to a focus centered on functionality of neural circuits,”
added David Kleinfeld, a professor of physics at UCSD. “Also,
this circuit could serve as a model system to deepen our understanding
of a pathology in the human eyeblink circuit.”

The only neural circuits
controlling reflexes that had been identified prior to the UCSD
physicists’ discovery were negative feedback loops, in
which sensory input leads to motor output that withdraws sensors
from the source of a stimulus. For example, such a reflex occurs
if you accidentally touch a hot stove.

On the other hand,
the newly discovered reflex circuit that controls rats’
whiskers as rats explore their environment is a positive feedback
loop. It helps rats keep their whiskers on an object, enabling
them to gather an uninterrupted stream of sensory information.

Nguyen commented that
positive feedback loops make engineers “squeamish”
because, if uncontrolled, they can create a vicious cycle. For
example, in a furnace controlled by positive feedback, rather
than negative feedback, the warmer a room became the more the
thermostat would signal the furnace to turn on.

This type of vicious
cycle appears to occur in blepharospasm. Normally, the blinking
reflex protects the eye from bright light and other environmental
hazards, but in blepharospasm this blinking response gets out
of control. The resulting muscle spasms can be so intense that
the eyelids remain forcefully closed for several hours at a
time.

“The human eyeblink
reflex circuit appears to share a common anatomy and physiology
with the neural circuit that controls rat whiskers,” said
Kleinfeld. “Actually, it isn’t unusual to see the
repetition of neural circuits with the same design principles
in different systems.”

As with blinking in
humans, rat whisking does not normally turn into a vicious cycle.
However, certain chemicals that interfere with normal communication
between nerve cells can cause unintentional whisking in rats.
By studying what mechanisms usually keep rat whisker movements
in check, researchers can develop a better understanding of
what causes the eyeblink reflex to go awry.

“Until now, treatment
for blepharospasm has been mostly trial and error,” said
Nguyen. “Our findings should permit a more principled
approach to the development of new medications and therapies.”

The researchers also
said their findings underscore the importance of basic scientific
research. Nguyen called the connection to blepharospasm a “serendipitous”
outcome of their work. Kleinfeld added that their finding is
just one example that shows the growing trend to fund research
on diseases at the expense of basic science may be unwise and
counterproductive.

“We need to understand
how a system works when it is normal in order to understand
what goes wrong when it is broken,” he said.

Their research was
supported by grants from the National Institutes of Health and
the Human Frontiers Scientific Program.